Use Of C1 Inhibitor For The Prevention Of Ischemia-Reperfusion Injury

• US 20130244941A1
• Filed: 02/25/2013
• Published: 09/19/2013
• Est. Priority Date: 12/21/2005
• Status: Active Grant

• Current Assignee: Pharming Intellectual Property B.V. (Pharming Group N.V.)
• Original Assignee: Pharming Intellectual Property B.V. (Pharming Group N.V.)
• Inventors: Mannesse, Maurice, Nuijens, Johannes Henricus, Pieper, Frank, De Simoni, Maria Grazia, Ziere, Gijsbertus Johannes
• Granted Patent: US 9,211,318 B2
• Time in Patent Office: Days
• US Class Current: 514/15.3
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to the therapeutic and prophylactic use of C1 inhibitor for preventing, reducing and treating ischemia and reperfusion injury. The C1 inhibitor of the present invention is still therapeutically effective when administered after an ischemic period and reperfusion and therefore particularly useful for unforeseen occurrences of ischemic reperfusion such as e.g. a stroke.

Claims

1-20. -20. (canceled)

21. A method of preventing, reducing, or treating pancreatitis in a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising an effective amount of a C1 inhibitor, wherein said C1 inhibitor has a plasma half-life in said subject that is less than plasma derived human C1 inhibitor.

22. A method according to claim 21, wherein said C1 inhibitor has a plasma half-life in said subject that is less than 6 hours.

23. A method according to claim 21, wherein said C1 inhibitor is administered in combination with a thrombolytic agent or after treatment with such agent.

24. A method according to claim 21, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 50 to about 2000 U/kg body weight of said subject.

25. A method according to claim 24, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 100 to about 1000 U/kg body weight of said subject.

26. A method according to claim 25, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 200 to about 800 U/kg body weight of said subject.

27. A method according to claim 26, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 400 to about 700 U/kg body weight of said subject.

28. A method according to claim 27, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 500 to about 700 U/kg body weight of said subject.

29. A method according to claim 21, wherein said recombinant human C1 inhibitor is administered to said subject in more than one dose in a 24-hour period.

30. A method according to claim 29, wherein each dose of said recombinant human C1 inhibitor is from about 50 to about 2000 U/kg body weight of said subject.

31. A method according to claim 30, wherein each dose of said recombinant human C1 inhibitor is from about 100 to about 1000 U/kg body weight of said subject.

32. A method according to claim 31, wherein each dose of said recombinant human C1 inhibitor is from about 200 to about 800 U/kg body weight of said subject.

33. A method according to claim 32, wherein each dose of said recombinant human C1 inhibitor is from about 400 to about 700 U/kg body weight of said subject.

34. A method according to claim 33, wherein each dose of said recombinant human C1 inhibitor is from about 500 to about 700 U/kg body weight of said subject.

35. A method according to claim 21, wherein said C1 inhibitor is a recombinant human C1 inhibitor obtained from a genetically engineered cell or organism.

36. A method of preventing, reducing, or treating pancreatitis in a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising an effective amount of a C1 inhibitor, wherein said C1 inhibitor has a reduced level of terminal sialic acid residues compared to plasma derived human C1 inhibitor.

37. A method according to claim 36, wherein said C1 inhibitor has a plasma half-life in said subject that is less than 6 hours.

38. A method according to claim 36, wherein said C1 inhibitor is administered in combination with a thrombolytic agent or after treatment with such agent.

39. A method according to claim 36, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 50 to about 2000 U/kg body weight of said subject.

40. A method according to claim 39, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 100 to about 1000 U/kg body weight of said subject.

41. A method according to claim 40, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 200 to about 800 U/kg body weight of said subject.

42. A method according to claim 41, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 400 to about 700 U/kg body weight of said subject.

43. A method according to claim 42, wherein the total amount of said recombinant human C1 inhibitor administered to said subject in a 24-hour period is from about 500 to about 700 U/kg body weight of said subject.

44. A method according to claim 36, wherein said recombinant human C1 inhibitor is administered to said subject in more than one dose in a 24-hour period.

45. A method according to claim 44, wherein each dose of said recombinant human C1 inhibitor is from about 50 to about 2000 U/kg body weight of said subject.

46. A method according to claim 45, wherein each dose of said recombinant human C1 inhibitor is from about 100 to about 1000 U/kg body weight of said subject.

47. A method according to claim 46, wherein each dose of said recombinant human C1 inhibitor is from about 200 to about 800 U/kg body weight of said subject.

48. A method according to claim 47, wherein each dose of said recombinant human C1 inhibitor is from about 400 to about 700 U/kg body weight of said subject.

49. A method according to claim 48, wherein each dose of said recombinant human C1 inhibitor is from about 500 to about 700 U/kg body weight of said subject.

50. A method according to claim 36, wherein said C1 inhibitor is a recombinant human C1 inhibitor obtained from a genetically engineered cell or organism.